Safety of ovarian tissue transplantation in patients with borderline ovarian tumors

• Published in: Human reproduction (Oxford) Vol. 33; no. 2; pp. 212 - 219
• Main Authors: Masciangelo, Rossella, Bosisio, Chiara, Donnez, Jacques, Amorim, Christiani A, Dolmans, Marie-Madeleine
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.02.2018
• Subjects: Adult; Animals; Cryopreservation; Female; Fertility Preservation - adverse effects; Fertility Preservation - methods; Humans; Immunohistochemistry; Keratin-7 - genetics; Keratin-7 - metabolism; Mice; Mice, SCID; Mucin-1 - genetics; Mucin-1 - metabolism; Ovarian Neoplasms - metabolism; Ovarian Neoplasms - pathology; Ovarian Neoplasms - surgery; Ovary - metabolism; Ovary - pathology; Ovary - transplantation; Prospective Studies; Reverse Transcriptase Polymerase Chain Reaction; Safety; Tissue Transplantation - adverse effects; Tissue Transplantation - methods; Transplantation, Heterologous; allografting; minimal residual disease; ovarian metastasis; ovarian tissue cryopreservation; fertility preservation; borderline ovarian tumor
• ISSN: 0268-1161; 1460-2350; 1460-2350
• DOI: 10.1093/humrep/dex352

Abstract STUDY QUESTION Is transplantation of cryopreserved ovarian tissue from patients with borderline ovarian tumors (BOTs) a safe procedure? SUMMARY ANSWER BOT cells were found in frozen-thawed and xenografted ovarian tissue in 1 of 11 BOT patients. WHAT IS KNOWN ALREADY The risk of reintroducing malignant cells upon ovarian tissue transplantation has been subject of debate for many years. Reimplantation of cryopreserved ovarian tissue from leukemia patients is unsafe, while results from studies of cryopreserved ovarian tissue from other forms of cancer, such as Hodgkin's lymphoma, are reassuring. STUDY DESIGN, SIZE, DURATION Prospective experimental study conducted in an academic research unit using ovarian tissue from 11 patients undergoing cryopreservation for BOTs. PARTICIPANTS/MATERIALS, SETTING, METHODS Histology, immunohistochemistry (IHC) for mucin 1 (MUC1) and cytokeratin 7 (CK7) and molecular analysis by reverse transcription quantitative polymerase chain reaction (RT-qPCR) for CK7 and MUC1 were performed on frozen-thawed ovarian tissue from 11 patients. Long-term (5 months) xenografting of ovarian tissue in immunodeficient mice was performed. The xenografts were analyzed by histology, IHC and RT-qPCR, furthermore IHC for CD10, a marker of endometriosis, was performed on a selected sample. MAIN RESULTS AND THE ROLE OF CHANCE Analysis by histology, IHC and RT-qPCR indicated 10 of the ovarian tissue samples were negative. Analysis of the xenograft samples indicated nine were negative for malignant cells but in two xenografts glandular lesions were detected by histology. In these two xenografts, CK7 and MUC1 markers were demonstrated by IHC and CK7 expression also by RT-qPCR. A BOT was confirmed in the xenograft in which the original ovarian tissue was positive, while in the other case IHC demonstrated expression of endometriosis marker CD10. LIMITATIONS, REASONS FOR CAUTION Cryopreserved ovarian fragments cannot be tested before transplantation, therefore the preimplantation analysis cannot guarantee that all cryopreserved fragments will be free of BOT cells. WIDER IMPLICATIONS OF THE FINDINGS BOT cells can be found in cryopreserved ovarian tissue from BOT patients, therefore preimplantation analysis is an absolute prerequisite. Endometriosis can also be detected in cryopreserved ovarian tissue and caution should also be exercised in this scenario. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by grants from the Fonds National de la Recherche Scientifique de Belgique (FNRS-PDR Convention T.0077.14, Télévie Grant 7.4590.16 awarded to Rossella Masciangelo, and Grant 5/4/150/5 awarded to Marie-Madeleine Dolmans), the Fonds Speciaux de Recherche, and the Foundation Against Cancer. None of the authors have any conflicting interests to declare.